Molecules. 2023 Sep 20;28(18):6726. doi: 10.3390/molecules28186726.

ABSTRACT

Neuronal models are an important tool in neuroscientific research. Hydrogen peroxide (H2O2), a major risk factor of neuronal oxidative stress, initiates a cascade of neuronal cell death. Polygonum minus Huds, known as 'kesum', is widely used in traditional medicine. P. minus has been reported to exhibit a few medicinal and pharmacological properties. The current study aimed to investigate the neuroprotective effects of P. minus ethanolic extract (PMEE) on H2O2-induced neurotoxicity in SH-SY5Y cells. LC-MS/MS revealed the presence of 28 metabolites in PMEE. Our study showed that the PMEE provided neuroprotection against H2O2-induced oxidative stress by activating the Nrf2/ARE, NF-κB/IκB and MAPK signaling pathways in PMEE pre-treated differentiated SH-SY5Y cells. Meanwhile, the acetylcholine (ACH) level was increased in the oxidative stress-induced treatment group after 4 h of exposure with H2O2. Molecular docking results with acetylcholinesterase (AChE) depicted that quercitrin showed the highest docking score at -9.5 kcal/mol followed by aloe-emodin, afzelin, and citreorosein at -9.4, -9.3 and -9.0 kcal/mol, respectively, compared to the other PMEE's identified compounds, which show lower docking scores. The results indicate that PMEE has neuroprotective effects on SH-SY5Y neuroblastoma cells in vitro. In conclusion, PMEE may aid in reducing oxidative stress as a preventative therapy for neurodegenerative diseases.

PMID:37764502 | DOI:10.3390/molecules28186726

Microorganisms. 2023 Sep 15;11(9):2328. doi: 10.3390/microorganisms11092328.

ABSTRACT

Aerobic granulation is an emerging process in wastewater treatment that has the potential to accelerate sedimentation of the microbial biomass during secondary treatment. Aerobic granulation has been difficult to achieve in the continuous flow reactors (CFRs) used in modern wastewater treatment plants. Recent research has demonstrated that the alternation of nutrient-abundant (feast) and nutrient-limiting (famine) conditions is able to promote aerobic granulation in a CFR. In this study, we conducted a metagenomic analysis with the objective of characterizing the bacterial composition of the granular biomass developed in three simulated plug flow reactors (PFRs) with different feast-to-famine ratios. Phylogenetic analyses revealed a clear distinction between the bacterial composition of aerobic granules in the pilot simulated PFRs as compared with conventional activated sludge. Larger and denser granules, showing improved sedimentation properties, were observed in the PFR with the longest famine time and were characterized by a greater proportion of bacteria producing abundant extracellular polymeric substances (EPS). Functional metagenomic analysis based on KEGG pathways indicated that the large and dense aerobic granules in the PFR with the longest famine time showed increased functionalities related to secretion systems and quorum sensing, which are characteristics of bacteria in biofilms and aerobic granules. This study contributes to a further understanding of the relationship between aerobic granule morphology and the bacterial composition of the granular biomass.

PMID:37764172 | DOI:10.3390/microorganisms11092328

Microorganisms. 2023 Aug 24;11(9):2149. doi: 10.3390/microorganisms11092149.

ABSTRACT

Secondary metabolites are not essential for the growth of microorganisms, but they play a critical role in how microbes interact with their surroundings. In addition to this important ecological role, secondary metabolites also have a variety of agricultural, medicinal, and industrial uses, and thus the examination of secondary metabolism of plants and microbes is a growing scientific field. While the chemical production of certain secondary metabolites is possible, industrial-scale microbial production is a green and economically attractive alternative. This is even more true, given the advances in bioengineering that allow us to alter the workings of microbes in order to increase their production of compounds of interest. This type of engineering requires detailed knowledge of the "chassis" organism's metabolism. Since the resources and the catalytic capacity of enzymes in microbes is finite, it is important to examine the tradeoffs between various bioprocesses in an engineered system and alter its working in a manner that minimally perturbs the robustness of the system while allowing for the maximum production of a product of interest. The in silico multi-objective analysis of metabolism using genome-scale models is an ideal method for such examinations.

PMID:37763993 | DOI:10.3390/microorganisms11092149

Life (Basel). 2023 Sep 7;13(9):1878. doi: 10.3390/life13091878.

ABSTRACT

The prediction of drug combinations is of great clinical significance. In many diseases, such as high blood pressure, diabetes, and stomach ulcers, the simultaneous use of two or more drugs has shown clear efficacy. It has greatly reduced the progression of drug resistance. This review presents the latest applications of methods for predicting the effects of drug combinations and the bioactivity databases commonly used in drug combination prediction. These studies have played a significant role in developing precision therapy. We first describe the concept of synergy. we study various publicly available databases for drug combination prediction tasks. Next, we introduce five algorithms applied to drug combinatorial prediction, which include traditional machine learning methods, deep learning methods, mathematical methods, systems biology methods and search algorithms. In the end, we sum up the difficulties encountered in prediction models.

PMID:37763281 | DOI:10.3390/life13091878

Int J Mol Sci. 2023 Sep 16;24(18):14171. doi: 10.3390/ijms241814171.

ABSTRACT

In the rapidly evolving landscape of molecular genetics and genomics, this Special Issue brings together a collection of insightful review articles that delve into the forefront of scientific exploration [...].

PMID:37762474 | DOI:10.3390/ijms241814171

Int J Mol Sci. 2023 Sep 14;24(18):14061. doi: 10.3390/ijms241814061.

ABSTRACT

Drug-target interactions (DTIs) are considered a crucial component of drug design and drug discovery. To date, many computational methods were developed for drug-target interactions, but they are insufficiently informative for accurately predicting DTIs due to the lack of experimentally verified negative datasets, inaccurate molecular feature representation, and ineffective DTI classifiers. Therefore, we address the limitations of randomly selecting negative DTI data from unknown drug-target pairs by establishing two experimentally validated datasets and propose a capsule network-based framework called CapBM-DTI to capture hierarchical relationships of drugs and targets, which adopts pre-trained bidirectional encoder representations from transformers (BERT) for contextual sequence feature extraction from target proteins through transfer learning and the message-passing neural network (MPNN) for the 2-D graph feature extraction of compounds to accurately and robustly identify drug-target interactions. We compared the performance of CapBM-DTI with state-of-the-art methods using four experimentally validated DTI datasets of different sizes, including human (Homo sapiens) and worm (Caenorhabditis elegans) species datasets, as well as three subsets (new compounds, new proteins, and new pairs). Our results demonstrate that the proposed model achieved robust performance and powerful generalization ability in all experiments. The case study on treating COVID-19 demonstrates the applicability of the model in virtual screening.

PMID:37762364 | DOI:10.3390/ijms241814061

Int J Mol Sci. 2023 Sep 13;24(18):14049. doi: 10.3390/ijms241814049.

ABSTRACT

We tested a hypothesis that in silico-discovered compounds targeting traumatic brain injury (TBI)-induced transcriptomics dysregulations will mitigate TBI-induced molecular pathology and augment the effect of co-administered antiseizure treatment, thereby alleviating functional impairment. In silico bioinformatic analysis revealed five compounds substantially affecting TBI-induced transcriptomics regulation, including calpain inhibitor, chlorpromazine, geldanamycin, tranylcypromine, and trichostatin A (TSA). In vitro exposure of neuronal-BV2-microglial co-cultures to compounds revealed that TSA had the best overall neuroprotective, antioxidative, and anti-inflammatory effects. In vivo assessment in a rat TBI model revealed that TSA as a monotherapy (1 mg/kg/d) or in combination with the antiseizure drug levetiracetam (LEV 150 mg/kg/d) mildly mitigated the increase in plasma levels of the neurofilament subunit pNF-H and cortical lesion area. The percentage of rats with seizures during 0-72 h post-injury was reduced in the following order: TBI-vehicle 80%, TBI-TSA (1 mg/kg) 86%, TBI-LEV (54 mg/kg) 50%, TBI-LEV (150 mg/kg) 40% (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 30% (p < 0.05). Cumulative seizure duration was reduced in the following order: TBI-vehicle 727 ± 688 s, TBI-TSA 898 ± 937 s, TBI-LEV (54 mg/kg) 358 ± 715 s, TBI-LEV (150 mg/kg) 42 ± 64 (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 109 ± 282 s (p < 0.05). This first preclinical intervention study on post-TBI acute seizures shows that a combination therapy with the tissue recovery enhancer TSA and LEV was safe but exhibited no clear benefit over LEV monotherapy on antiseizure efficacy. A longer follow-up is needed to confirm the possible beneficial effects of LEV monotherapy and combination therapy with TSA on chronic post-TBI structural and functional outcomes, including epileptogenesis.

PMID:37762352 | DOI:10.3390/ijms241814049

Genes (Basel). 2023 Aug 30;14(9):1735. doi: 10.3390/genes14091735.

ABSTRACT

BACKGROUND: Stem cells have been associated with self-renewing and plasticity and have been investigated in various odontogenic lesions in association with their pathogenesis and biological behavior. We aim to provide a systematic review of stem cell markers' expression in odontogenic tumors and cysts.

METHODS: The literature was searched through the MEDLINE/PubMed, EMBASE via OVID, Web of Science, and CINHAL via EBSCO databases for original studies evaluating stem cell markers' expression in different odontogenic tumors/cysts, or an odontogenic disease group and a control group. The studies' risk of bias (RoB) was assessed via a Joanna Briggs Institute Critical Appraisal Tool. Meta-analysis was conducted for markers evaluated in the same pair of odontogenic tumors/cysts in at least two studies.

RESULTS: 29 studies reported the expression of stem cell markers, e.g., SOX2, OCT4, NANOG, CD44, ALDH1, BMI1, and CD105, in various odontogenic lesions, through immunohistochemistry/immunofluorescence, polymerase chain reaction, flow cytometry, microarrays, and RNA-sequencing. Low, moderate, and high RoBs were observed in seven, nine, and thirteen studies, respectively. Meta-analysis revealed a remarkable discriminative ability of SOX2 for ameloblastic carcinomas or odontogenic keratocysts over ameloblastomas.

CONCLUSION: Stem cells might be linked to the pathogenesis and clinical behavior of odontogenic pathologies and represent a potential target for future individualized therapies.

PMID:37761874 | DOI:10.3390/genes14091735

Diagnostics (Basel). 2023 Sep 9;13(18):2893. doi: 10.3390/diagnostics13182893.

ABSTRACT

Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolytes and acid base. It is associated with poor prognosis and prolonged hospitalization. Therefore, an early diagnosis and treatment to avoid the severe AKI stage are important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for the early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.

PMID:37761260 | DOI:10.3390/diagnostics13182893

Foods. 2023 Sep 18;12(18):3470. doi: 10.3390/foods12183470.

ABSTRACT

(1) Background: The chicken egg is an animal product of great agronomic interest. The egg white and yolk constitute high-quality protein sources for humans with high digestibility and well-balanced amino acid profiles. Despite the egg white and yolk protein's undisputed value, research to unravel their full proteome content and its properties is still ongoing. We aimed to exhaustively analyze the proteome of egg white and yolk by applying intrinsic proteomics and bioinformatics approaches in order to unravel the full protein potential of this landmark food. (2) Methods: A total of 45 freshly laid, unfertilized, chicken eggs were subjected to nanoLC-MS/MS Orbitrap analysis following a peptide pre-fractionation step. A comprehensive bioinformatics processing step was undertaken towards elucidating potential activities and roles of identified molecules. In parallel, the literature was mined concerning all reported egg white and yolk protein identifications. (3) Results: Our analysis revealed 371 and 428 new proteins, reported for the first time to be present in the egg white and yolk, respectively. From the bioactivity standpoint, egg white and yolk proteins showed high enrichment for antioxidant and anti-inflammatory processes, while exerting high relevance for the apoptosis and focal adhesion pathways. (4) Conclusions: Egg white and yolk proteins exert diverse and multifaceted properties. A total of 799 proteins were reported for the first time as being part of the egg and yolk. Our novel protein data enriched those already published in the literature and the first ever chicken egg white and yolk Protein Atlas, comprising 1392 protein entries, was generated. This dataset will provide a cornerstone reference for future studies involving egg proteins.

PMID:37761179 | DOI:10.3390/foods12183470

Foods. 2023 Sep 15;12(18):3433. doi: 10.3390/foods12183433.

ABSTRACT

This study provides an accurate economic characterization of the supply of edible mushrooms throughout Italy within the European context to fill the relevant research gap and highlight barriers and opportunities that are consistent with the Sustainable Development Goals. Italian companies operating in this field were identified and economically characterized using the Chamber of Commerce's Register of Companies. A qualitative web content analysis was then conducted to extract information about the marketed products, mushroom species, and retail channels, as well as the adopted certifications. The obtained data were quantitatively analyzed through descriptive statistics and multiple correspondence analysis. The Italian market is concentrated in northern areas of the country, and the limited company size indicates fragmentation at the production level, which led to Italy not being competitive enough and, thus, heavily rely on imports. Production is limited to less than 10 species, and innovative mushroom-based products, such as burgers, have shown a limited presence on the market, although they are gaining market share online. The novelty of growing kits highlights the potential to use food production waste to create fungal substrates. Investments in training new mushroom growers and studying new formulations and new fungal species are needed; these investments could allow greater market differentiation and be a good opportunity to promote local economies and create new job opportunities, thus meeting the requirements for sustainable development.

PMID:37761142 | DOI:10.3390/foods12183433

Antibiotics (Basel). 2023 Sep 6;12(9):1410. doi: 10.3390/antibiotics12091410.

ABSTRACT

The antimicrobial activity of SJGAP (skipjack tuna GAPDH-related antimicrobial peptide) and four chemical analogs thereof was determined under different physicochemical conditions, including different pH values, the presence of monovalent and divalent cations, and after a heating treatment. The toxicity of these five peptides was also studied with hemolytic activity assays, while their stability under human gastrointestinal conditions was evaluated using a dynamic in vitro digestion model and chromatographic and mass spectrometric analyses. The antibacterial activity of all analogs was found to be inhibited by the presence of divalent cations, while monovalent cations had a much less pronounced impact, even promoting the activity of the native SJGAP. The peptides were also more active at acidic pH values, but they did not all show the same stability following a heat treatment. SJGAP and its analogs did not show significant hemolytic activity (except for one of the analogs at a concentration equivalent to 64 times that of its minimum inhibitory concentration), and the two analogs whose digestibility was studied degraded very rapidly once they entered the stomach compartment of the digestion model. This study highlights for the first time the characteristics of antimicrobial peptides from Scombridae or homologous to GAPDH that are directly related to their potential clinical or food applications.

PMID:37760707 | DOI:10.3390/antibiotics12091410

Antibiotics (Basel). 2023 Sep 1;12(9):1396. doi: 10.3390/antibiotics12091396.

ABSTRACT

The discovery of new antimicrobials is necessary to combat multidrug-resistant (MDR) bacteria, especially those that infect wounds and form prodigious biofilms, such as Acinetobacter baumannii. Antimicrobial peptides (AMPs) are a promising class of new therapeutics against drug-resistant bacteria, including gram-negatives. Here, we utilized a computational AMP design strategy combining database filtering technology plus positional analysis to design a series of novel peptides, named HRZN, designed to be active against A. baumannii. All of the HRZN peptides we synthesized exhibited antimicrobial activity against three MDR A. baumannii strains with HRZN-15 being the most active (MIC 4 µg/mL). This peptide also inhibited and eradicated biofilm of A. baumannii strain AB5075 at 8 and 16 µg/mL, which is highly effective. HRZN-15 permeabilized and depolarized the membrane of AB5075 rapidly, as demonstrated by the killing kinetics. HRZN 13 and 14 peptides had little to no hemolysis activity against human red blood cells, whereas HRZN-15, -16, and -17 peptides demonstrated more significant hemolytic activity. HRZN-15 also demonstrated toxicity to waxworms. Further modification of HRZN-15 could result in a new peptide with an improved toxicity profile. Overall, we successfully designed a set of new AMPs that demonstrated activity against MDR A. baumannii using a computational approach.

PMID:37760693 | DOI:10.3390/antibiotics12091396

Antibiotics (Basel). 2023 Aug 25;12(9):1367. doi: 10.3390/antibiotics12091367.

ABSTRACT

Mycobacterium tuberculosis (Mtb) acquires drug resistance at a rate comparable to that of bacterial pathogens that replicate much faster and have a higher mutation rate. One explanation for this rapid acquisition of drug resistance in Mtb is that drug resistance may evolve in other fast-replicating mycobacteria and then be transferred to Mtb through horizontal gene transfer (HGT). This paper aims to address three questions. First, does HGT occur between Mtb and other mycobacterial species? Second, what genes after HGT tend to survive in the recipient genome? Third, does HGT contribute to antibiotic resistance in Mtb? I present a conceptual framework for detecting HGT and analyze 39 ribosomal protein genes, 23S and 16S ribosomal RNA genes, as well as several genes targeted by antibiotics against Mtb, from 43 genomes representing all major groups within Mycobacterium. I also included mgtC and the insertion sequence IS6110 that were previously reported to be involved in HGT. The insertion sequence IS6110 shows clearly that the Mtb complex participates in HGT. However, the horizontal transferability of genes depends on gene function, as was previously hypothesized. HGT is not observed in functionally important genes such as ribosomal protein genes, rRNA genes, and other genes chosen as drug targets. This pattern can be explained by differential selection against functionally important and unimportant genes after HGT. Functionally unimportant genes such as IS6110 are not strongly selected against, so HGT events involving such genes are visible. For functionally important genes, a horizontally transferred diverged homologue from a different species may not work as well as the native counterpart, so the HGT event involving such genes is strongly selected against and eliminated, rendering them invisible to us. In short, while HGT involving the Mtb complex occurs, antibiotic resistance in the Mtb complex arose from mutations in those drug-targeted genes within the Mtb complex and was not gained through HGT.

PMID:37760664 | DOI:10.3390/antibiotics12091367

Animals (Basel). 2023 Sep 16;13(18):2941. doi: 10.3390/ani13182941.

ABSTRACT

A new species of the subfamily Pselaphinae (Coleoptera: Staphylinidae) has been discovered on Mount Etna (Sicily, Italy) and is described herein as Bryaxis aetnensis sp. nov. The new species is closely associated with the Bryaxis difficilis group, a highly homogeneous group of species living in the regions of Sicily and Sardinia. Diagnostic features and distribution of Sicilian species of this group are treated and illustrated herein. Bryaxis aetnensis sp. nov. exhibits similarities to B. marinae but can be distinguished by the darker color, longer antennal scape and terminal palpomere, and in the aedeagus morphology. The distribution of B. aetnensis sp. nov. spans a wide altitudinal range, demonstrating a remarkable climatic tolerance across the slopes and diverse habitats of Mount Etna. This broad tolerance reflects the species' probable high ecological plasticity, which may also contribute to the observed morphological variability among individuals from different sampling sites. The significance of this new discovery on Mount Etna highlights the need to intensify sampling efforts in the region. Strengthening protection for these unexplored environments is crucial, and it also aids in unraveling biogeographic questions about the fauna inhabiting the area. As a relatively young volcanic environment, species colonization has occurred recently, making it an intriguing subject of investigation.

PMID:37760341 | DOI:10.3390/ani13182941

Animals (Basel). 2023 Sep 7;13(18):2848. doi: 10.3390/ani13182848.

ABSTRACT

Scent-marking through odours from excreta and glandular secretions is widespread in mammals. Among primates, diurnal group-living lemurs show different deployment modalities as part of their strategy to increase signal detection. We studied the diademed sifaka (Propithecus diadema) in the Maromizaha New Protected Area, Eastern Madagascar. We tested whether the scent-marking deposition occurred using a sequential rubbing of different body parts. We also tested if glands (i.e., deposition of glandular secretions) were more frequently rubbed than genital orifices (i.e., deposition of excreta) by comparing different kinds of rubbing behaviour. We then investigated if the depositor's rank and sex affected the sequence of rubbing behaviour, the height at which the scent-marking happened, and the tree part targeted. We found that glandular secretions were often deposited with urine, especially in dominant individuals. The probability of anogenital and chest marking was highest, but chest rubbing most frequently occurred in dominant males. Markings were deposited at similar heights across age and sex, and tree trunks were the most used substrate. Males exhibited long and more complex scent-marking sequences than females. Our results indirectly support the idea that diademed sifakas deploy a sex-dimorphic mixture of glandular secretions and excreta to increase the probability of signal detection by conspecifics.

PMID:37760248 | DOI:10.3390/ani13182848

Bioengineering (Basel). 2023 Sep 7;10(9):1056. doi: 10.3390/bioengineering10091056.

ABSTRACT

The current manuscript addresses the problem of parameter estimation for kinetic models of chemical reaction networks from observed time series partial experimental data of species concentrations. It is demonstrated how the Kron reduction method of kinetic models, in conjunction with the (weighted) least squares optimization technique, can be used as a tool to solve the above-mentioned ill-posed parameter estimation problem. First, a new trajectory-independent measure is introduced to quantify the dynamical difference between the original mathematical model and the corresponding Kron-reduced model. This measure is then crucially used to estimate the parameters contained in the kinetic model so that the corresponding values of the species' concentrations predicted by the model fit the available experimental data. The new parameter estimation method is tested on two real-life examples of chemical reaction networks: nicotinic acetylcholine receptors and Trypanosoma brucei trypanothione synthetase. Both weighted and unweighted least squares techniques, combined with Kron reduction, are used to find the best-fitting parameter values. The method of leave-one-out cross-validation is utilized to determine the preferred technique. For nicotinic receptors, the training errors due to the application of unweighted and weighted least squares are 3.22 and 3.61 respectively, while for Trypanosoma synthetase, the application of unweighted and weighted least squares result in training errors of 0.82 and 0.70 respectively. Furthermore, the problem of identifiability of dynamical systems, i.e., the possibility of uniquely determining the parameters from certain types of output, has also been addressed.

PMID:37760158 | DOI:10.3390/bioengineering10091056

Antioxidants (Basel). 2023 Sep 18;12(9):1775. doi: 10.3390/antiox12091775.

ABSTRACT

Non-small cell lung cancer (NSCLC) poses a significant global health burden with unsatisfactory survival rates, despite advancements in diagnostic and therapeutic modalities. Novel therapeutic approaches are urgently required to improve patient outcomes. Pharmacological ascorbate (P-AscH-; ascorbate at millimolar concentration in plasma) emerged as a potential candidate for cancer therapy for recent decades. In this present study, we explore the anti-cancer effects of P-AscH- on NSCLC and elucidate its underlying mechanisms. P-AscH- treatment induces formation of cellular oxidative distress; disrupts cellular bioenergetics; and leads to induction of apoptotic cell death and ultimately reduction in clonogenic survival. Remarkably, DNA and DNA damage response machineries are identified as vulnerable targets for P-AscH- in NSCLC therapy. Treatments with P-AscH- increase the formation of DNA damage and replication stress markers while inducing mislocalization of DNA repair machineries. The cytotoxic and genotoxic effects of P-AscH- on NSCLC were reversed by co-treatment with catalase, highlighting the roles of extracellular hydrogen peroxide in anti-cancer activities of P-AscH-. The data from this current research advance our understanding of P-AscH- in cancer treatment and support its potential clinical use as a therapeutic option for NSCLC therapy.

PMID:37760080 | DOI:10.3390/antiox12091775

Antioxidants (Basel). 2023 Sep 1;12(9):1709. doi: 10.3390/antiox12091709.

ABSTRACT

Griffonia simplicifolia, a tropical plant endemic to West Africa, is highly regarded for its significant pharmacological potential. The objective of this study was to evaluate the metabolomic profile and to explore the antioxidant properties, antiproliferative activity, and antimicrobial potential of G. simplicifolia seed extracts obtained through either maceration, microwave-assisted extraction (MAE), or Soxhlet extraction using water, acetone, methanol and ethanol as solvents. Overall, methanol possessed superior total extraction efficiency. HPLC analyses confirmed the efficacy of acetone and ethanol as optimal solvents for the extraction of flavonoids and flavan-3-ols, whereas MAE exhibited enhanced effectiveness in extracting N-containing compounds, including 5-hydroxytryptophan (5-HTP). HPLC-MS analyses identified forty-three compounds, including thirty-four phenolic compounds and nine N-containing molecules. Isomyricitrin, taxifolin and a flavonol glucuronide were the main polyphenols, whereas 5-HTP was the main N-containing compound. Hydroalcoholic G. simplicifolia extracts showed the highest radical scavenging and metal-reducing antioxidant power, suggesting that most of the contribution to antioxidant activity depends on the more polar bioactive compounds. G. simplicifolia extracts showed dose-dependent antiproliferative activity against three distinct cancer cell lines (HeLa, HepG2, and MCF-7), with notable variations observed among both the different extracts and cell lines and divergent GI50 values, emphasizing substantial discrepancies in cell sensitivity to the various extracts. Furthermore, G. simplicifolia extracts revealed antibiotic activity against Staphylococcus aureus. Our results highlight the potential of G. simplicifolia phytochemicals in the development of functional foods, nutraceuticals, and dietary supplements.

PMID:37760012 | DOI:10.3390/antiox12091709

Antioxidants (Basel). 2023 Sep 1;12(9):1707. doi: 10.3390/antiox12091707.

ABSTRACT

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and a theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 0.050 µM-4·s-1 and 0.055 s-1, respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation state to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.

PMID:37760010 | DOI:10.3390/antiox12091707